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The New England Journal of Medicine Jul 2016A 22-year-old woman reports having hirsutism and irregular menses. She describes unpredictable and infrequent menses (five or six per year) since menarche at 11 years of... (Review)
Review
A 22-year-old woman reports having hirsutism and irregular menses. She describes unpredictable and infrequent menses (five or six per year) since menarche at 11 years of age. Dark, coarse facial hair began to develop at 13 years of age. The symptoms worsened after she gained weight in college. The physical examination includes a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 29, blood pressure of 135/85 mm Hg, and moderate hirsutism without virilization. Laboratory tests reveal a total testosterone level of 65 ng per deciliter (2.3 nmol per liter) (assay reference range, 14 to 53 ng per deciliter [0.5 to 1.8 nmol per liter]), calculated free testosterone level of 15.3 pg per milliliter (53.1 pmol per liter) (assay reference range, 0.6 to 6.8 pg per milliliter [2.1 to 23.6 pmol per liter]), and glycated hemoglobin level of 5.7% (normal value, ≤5.6%). How should this case be evaluated and managed?
Topics: Contraceptives, Oral, Combined; Female; Hirsutism; Humans; Polycystic Ovary Syndrome; Young Adult
PubMed: 27406348
DOI: 10.1056/NEJMcp1514916 -
Nature Reviews. Gastroenterology &... Jan 2023Heavy alcohol consumption is a major cause of morbidity and mortality. Globally, alcohol per-capita consumption rose from 5.5 litres in 2005 to 6.4 litres in 2016... (Review)
Review
Heavy alcohol consumption is a major cause of morbidity and mortality. Globally, alcohol per-capita consumption rose from 5.5 litres in 2005 to 6.4 litres in 2016 and is projected to increase further to 7.6 litres in 2030. In 2019, an estimated 25% of global cirrhosis deaths were associated with alcohol. The global estimated age-standardized death rate (ASDR) of alcohol-associated cirrhosis was 4.5 per 100,000 population, with the highest and lowest ASDR in Africa and the Western Pacific, respectively. The annual incidence of hepatocellular carcinoma (HCC) among patients with alcohol-associated cirrhosis ranged from 0.9% to 5.6%. Alcohol was associated with approximately one-fifth of global HCC-related deaths in 2019. Between 2012 and 2017, the global estimated ASDR for alcohol-associated cirrhosis declined, but the ASDR for alcohol-associated liver cancer increased. Measures are required to curb heavy alcohol consumption to reduce the burden of alcohol-associated cirrhosis and HCC. Degree of alcohol intake, sex, older age, obesity, type 2 diabetes mellitus, gut microbial dysbiosis and genetic variants are key factors in the development of alcohol-associated cirrhosis and HCC. In this Review, we discuss the global epidemiology, projections and risk factors for alcohol-associated cirrhosis and HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Diabetes Mellitus, Type 2; Risk Factors; Liver Cirrhosis, Alcoholic; Liver Cirrhosis; Ethanol; Incidence
PubMed: 36258033
DOI: 10.1038/s41575-022-00688-6 -
The New England Journal of Medicine Jan 2015Hyperkalemia (serum potassium level, >5.0 mmol per liter) is associated with increased mortality among patients with heart failure, chronic kidney disease, or diabetes.... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Hyperkalemia (serum potassium level, >5.0 mmol per liter) is associated with increased mortality among patients with heart failure, chronic kidney disease, or diabetes. We investigated whether sodium zirconium cyclosilicate (ZS-9), a novel selective cation exchanger, could lower serum potassium levels in patients with hyperkalemia.
METHODS
In this multicenter, two-stage, double-blind, phase 3 trial, we randomly assigned 753 patients with hyperkalemia to receive either ZS-9 (at a dose of 1.25 g, 2.5 g, 5 g, or 10 g) or placebo three times daily for 48 hours. Patients with normokalemia (serum potassium level, 3.5 to 4.9 mmol per liter) at 48 hours were randomly assigned to receive either ZS-9 or placebo once daily on days 3 to 14 (maintenance phase). The primary end point was the exponential rate of change in the mean serum potassium level at 48 hours.
RESULTS
At 48 hours, the mean serum potassium level had decreased from 5.3 mmol per liter at baseline to 4.9 mmol per liter in the group of patients who received 2.5 g of ZS-9, 4.8 mmol per liter in the 5-g group, and 4.6 mmol per liter in the 10-g group, for mean reductions of 0.5, 0.5, and 0.7 mmol per liter, respectively (P<0.001 for all comparisons) and to 5.1 mmol per liter in the 1.25-g group and the placebo group (mean reduction, 0.3 mmol per liter). In patients who received 5 g of ZS-9 and those who received 10 g of ZS-9, serum potassium levels were maintained at 4.7 mmol per liter and 4.5 mmol per liter, respectively, during the maintenance phase, as compared with a level of more than 5.0 mmol per liter in the placebo group (P<0.01 for all comparisons). Rates of adverse events were similar in the ZS-9 group and the placebo group (12.9% and 10.8%, respectively, in the initial phase; 25.1% and 24.5%, respectively, in the maintenance phase). Diarrhea was the most common complication in the two study groups.
CONCLUSIONS
Patients with hyperkalemia who received ZS-9, as compared with those who received placebo, had a significant reduction in potassium levels at 48 hours, with normokalemia maintained during 12 days of maintenance therapy. (Funded by ZS Pharma; ClinicalTrials.gov number, NCT01737697.).
Topics: Adult; Aged; Diabetes Complications; Disease-Free Survival; Double-Blind Method; Female; Heart Failure; Humans; Hyperkalemia; Male; Middle Aged; Potassium; Prospective Studies; Renal Insufficiency, Chronic; Renin-Angiotensin System; Secondary Prevention; Silicates
PubMed: 25415807
DOI: 10.1056/NEJMoa1411487 -
The New England Journal of Medicine Sep 2017In some patients with moderate-to-severe asthma, particularly those with noneosinophilic inflammation, the disease remains uncontrolled. This trial evaluated the... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
In some patients with moderate-to-severe asthma, particularly those with noneosinophilic inflammation, the disease remains uncontrolled. This trial evaluated the efficacy and safety of tezepelumab (AMG 157/MEDI9929), a human monoclonal antibody specific for the epithelial-cell-derived cytokine thymic stromal lymphopoietin (TSLP), in patients whose asthma remained uncontrolled despite treatment with long-acting beta-agonists and medium-to-high doses of inhaled glucocorticoids.
METHODS
In this phase 2, randomized, double-blind, placebo-controlled trial, we compared subcutaneous tezepelumab at three dose levels with placebo over a 52-week treatment period. The primary end point was the annualized rate of asthma exacerbations (events per patient-year) at week 52.
RESULTS
The use of tezepelumab at a dose of 70 mg every 4 weeks (low dose; 145 patients), 210 mg every 4 weeks (medium dose; 145 patients), or 280 mg every 2 weeks (high dose; 146 patients) resulted in annualized asthma exacerbation rates at week 52 of 0.26, 0.19, and 0.22, respectively, as compared with 0.67 in the placebo group (148 patients). Thus, exacerbation rates in the respective tezepelumab groups were lower by 61%, 71%, and 66% than the rate in the placebo group (P<0.001 for all comparisons). Similar results were observed in patients regardless of blood eosinophil counts at enrollment. The prebronchodilator forced expiratory volume in 1 second at week 52 was higher in all tezepelumab groups than in the placebo group (difference, 0.12 liters with the low dose [P=0.01], 0.11 liters with the medium dose [P=0.02], and 0.15 liters with the high dose [P=0.002]). A total of 2 patients in the medium-dose group, 3 in the high-dose group, and 1 in the placebo group discontinued the trial regimen because of adverse events.
CONCLUSIONS
Among patients treated with long-acting beta-agonists and medium-to-high doses of inhaled glucocorticoids, those who received tezepelumab had lower rates of clinically significant asthma exacerbations than those who received placebo, independent of baseline blood eosinophil counts. (Funded by MedImmune [a member of the AstraZeneca Group] and Amgen; PATHWAY ClinicalTrials.gov number, NCT02054130 .).
Topics: Administration, Inhalation; Adrenergic beta-Agonists; Adult; Anti-Asthmatic Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Asthma; Cytokines; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Eosinophils; Female; Glucocorticoids; Humans; Injections, Subcutaneous; Intention to Treat Analysis; Male; Middle Aged; Thymic Stromal Lymphopoietin
PubMed: 28877011
DOI: 10.1056/NEJMoa1704064 -
Turkish Journal of Medical Sciences Aug 2020Alcohol is a unique addictive substance used by many people for different reasons. Alcohol use affects not only the users but also the family and the whole society in a...
Alcohol is a unique addictive substance used by many people for different reasons. Alcohol use affects not only the users but also the family and the whole society in a negative way. Alcohol is one of the most commonly used substances for entertainment purposes in the world and 1 in 3 people is a current drinker. 2348 billion people (43% of the population) aged 15 and over are current drinkers and males drink about 2 times more frequently than females (53.6%/32.3%). According to the Global Alcohol and Health Report published by the World Health Organization (WHO) (2018), total alcohol per capita consumption (APC) worldwide aged 15 and over increased from 5.7 liters in 2000 to 6.4 liters in 2016. Harmful alcohol consumption is a major public health problem and it is known to be associated with more than 200 diseases and injuries. Policies and measures to prevent alcohol use are not implemented adequately and the burden of alcohol-related illnesses continues to increase tremendously. In order to prevent and reduce the harmful effects of alcohol, alcohol policies should be formulated based on the best evidence from a public health perspective.
Topics: Adolescent; Adult; Alcohol Drinking; Female; Health Policy; Humans; Male; Socioeconomic Factors; Young Adult
PubMed: 32421277
DOI: 10.3906/sag-2002-237 -
British Journal of Anaesthesia May 2018Pharmacokinetic (PK) and pharmacodynamic (PD) models are used in target-controlled-infusion (TCI) systems to determine the optimal drug administration to achieve a...
BACKGROUND
Pharmacokinetic (PK) and pharmacodynamic (PD) models are used in target-controlled-infusion (TCI) systems to determine the optimal drug administration to achieve a desired target concentration in a central or effect-site compartment. Our aim was to develop a PK-PD model for propofol that can predict the bispectral index (BIS) for a broad population, suitable for TCI applications.
METHODS
Propofol PK data were obtained from 30 previously published studies, five of which also contained BIS observations. A PK-PD model was developed using NONMEM. Weight, age, post-menstrual age (PMA), height, sex, BMI, and presence/absence of concomitant anaesthetic drugs were explored as covariates. The predictive performance was measured across young children, children, adults, elderly, and high-BMI individuals, and in simulated TCI applications.
RESULTS
Overall, 15 433 propofol concentration and 28 639 BIS observations from 1033 individuals (672 males and 361 females) were analysed. The age range was from 27 weeks PMA to 88 yr, and the weight range was 0.68-160 kg. The final model uses age, PMA, weight, height, sex, and presence/absence of concomitant anaesthetic drugs as covariates. A 35-yr-old, 170 cm, 70 kg male (without concomitant anaesthetic drugs) has a V, V, V, CL, Q, Q, and k of 6.28, 25.5, 273 litres, 1.79, 1.75, 1.11 litres min, and 0.146 min, respectively. The propofol TCI administration using the model matches well with recommendations for all age groups considered for both anaesthesia and sedation.
CONCLUSIONS
We developed a PK-PD model to predict the propofol concentrations and BIS for broad, diverse population. This should be useful for TCI in anaesthesia and sedation.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anesthesia; Anesthetics, Intravenous; Child; Child, Preschool; Female; Humans; Infant; Infusions, Intravenous; Male; Middle Aged; Models, Biological; Propofol; Young Adult
PubMed: 29661412
DOI: 10.1016/j.bja.2018.01.018 -
The New England Journal of Medicine Sep 2017The clinical effect of routine oxygen therapy in patients with suspected acute myocardial infarction who do not have hypoxemia at baseline is uncertain. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The clinical effect of routine oxygen therapy in patients with suspected acute myocardial infarction who do not have hypoxemia at baseline is uncertain.
METHODS
In this registry-based randomized clinical trial, we used nationwide Swedish registries for patient enrollment and data collection. Patients with suspected myocardial infarction and an oxygen saturation of 90% or higher were randomly assigned to receive either supplemental oxygen (6 liters per minute for 6 to 12 hours, delivered through an open face mask) or ambient air.
RESULTS
A total of 6629 patients were enrolled. The median duration of oxygen therapy was 11.6 hours, and the median oxygen saturation at the end of the treatment period was 99% among patients assigned to oxygen and 97% among patients assigned to ambient air. Hypoxemia developed in 62 patients (1.9%) in the oxygen group, as compared with 254 patients (7.7%) in the ambient-air group. The median of the highest troponin level during hospitalization was 946.5 ng per liter in the oxygen group and 983.0 ng per liter in the ambient-air group. The primary end point of death from any cause within 1 year after randomization occurred in 5.0% of patients (166 of 3311) assigned to oxygen and in 5.1% of patients (168 of 3318) assigned to ambient air (hazard ratio, 0.97; 95% confidence interval [CI], 0.79 to 1.21; P=0.80). Rehospitalization with myocardial infarction within 1 year occurred in 126 patients (3.8%) assigned to oxygen and in 111 patients (3.3%) assigned to ambient air (hazard ratio, 1.13; 95% CI, 0.88 to 1.46; P=0.33). The results were consistent across all predefined subgroups.
CONCLUSIONS
Routine use of supplemental oxygen in patients with suspected myocardial infarction who did not have hypoxemia was not found to reduce 1-year all-cause mortality. (Funded by the Swedish Heart-Lung Foundation and others; DETO2X-AMI ClinicalTrials.gov number, NCT01787110 .).
Topics: Aged; Female; Follow-Up Studies; Heart Diseases; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Oxygen Inhalation Therapy; Proportional Hazards Models; Registries; Sweden; Treatment Failure
PubMed: 28844200
DOI: 10.1056/NEJMoa1706222